Hoffmann Lab - Graded Implants and Regenerative Strategies

The group “Graded Implants and Regenerative Strategies” (www.lbb-mhh.de/index.php?id=1417) located within the department of Orthopaedic Surgery (Prof. Dr. H. Windhagen) and headed by Prof. Dr. Andrea Hoffmann performs basic research to investigate important factors involved in the function of human mesenchymal stem cells (MSCs). Through biochemical, molecular biological and cell biological methods the understanding of fundamental principles of stem cell functions under normal and inflammatory conditions shall be improved. The factors investigated contribute to maintenance of stem cell characteristics and the so-called potency of stem cells, or they guide differentiation of the stem cells into distinct cell types. This differentiation capacity can be altered in inflammatory conditions. “Factors” in narrower sense are genes or proteins, e.g. growth and transcription factors like bone morphogenetic proteins 2 (BMP2) or constitutively active Smad8, so-called surface antigens of cells or signal mediators like transforming growth factor-beta activated kinase 1 (TAK1) which control biological processes. “Factors” in the broader sense can also imply native or genetically modified (stem) cells.

Our aim is to develop procedures for isolation and cultivation of MSCs by improved materials, coatings, surface structuring or medium additives in the long term in order to enhance the clinical use of MSCs. We focus on the following questions:

  • characterization of biolocial and biochemical functions of factors

  • elucidation and targeted modification of signaling cascades for tissue development and tissue regeneration (differentiation)

  • investigation of inflammation and cytokine-dependent signal transduction events: interaction between TAK1 and signaling cascades for tissue development and regeneration

  • strategies for a (stem cell mediated) therapy of skeletal diseases like rheumatoid arthritis and osteoarthritis as well as for optimization of biomedical implants.

Although in principle we focus on basic research it is also our aim to elaborate translational strategies (“regenerative strategies”) based on our own research results and on MSCs, e.g. for optimization of medical implants. Alternatively, however, it is also envisaged to circumvent and replace cellular therapy by identification of novel factors. One exemplary approach is followed in a planned DFG-funded research unit to restore tendon-bone junctions based on a novel implant. Our research focusses on tissues of the musculo-skeletal system and in tight collaboration with the department of rhino-oto-laryngology within VIANNA also on the inner ear. Here, MSCs are modified with neurotrophic growth or transcription factors to use them as a drug delivery system for cochlea implants.

Projects

  • Characterization of MSCs: Biological functions of selected surface antigens

  • Characterization of MSCs: Biological functions of growth and transcription factors

  • Characterization of MSCs: Differentiation into bone, cartilage and tendon cells

  • Use of MSCs for cochlea implants: Development of a biohybrid electrode and novel biomaterials (DFG: SFB 599, HO 2058/10-1, HO 2058/13-1)

  • Use of a transcription factor and a growth factor for regeneration of tendon-bone junctions: Development of a biomimetic implant

  • The role of the enzyme (kinase) TAK1 in rheumatoid arthritis

  • Research Unit FOR 2180 (www.gradierte-implantate.de)

Cooperation partners

  • Hannover Medical School

    • Laryngology, Rhinology and Otology (Prof. T. Lenarz, PD Dr. A. Warnecke)
    • Neurology (Prof. M. Stangel, Prof. S. Petri)
    • Dental Prosthetics (Prof. M. Stiesch, Dr. A. Winkel)
    • Cellular Therapeutics (Prof. U. Köhl)
    • Physiological Chemistry (Prof. T. Tamura)
    • Transfusion Medicine (Prof. R. Blasczyk, PD Dr.T. Müller)
  • Leibniz Universität Hannover

    • Inorganic Chemistry (Prof. P. Behrens)
    • Multiphase Processes (Prof. B. Glasmacher)
    • LaserCentre Hannover (Prof. B. Chichkov)
    • Cellular Physiology and Cellular Mechanics (Prof. A. Ngezahayo)
    • Technical Chemistry (Prof. T. Scheper)
  • Tierärztliche Hochschule Hannover

    • Pathology (Prof. W. Baumgärtner)
  • Technische Universität Braunschweig

    • Technischal Chemistry (Prof. H. Menzel)
    • Pharmazeutical Chemistry (Prof. H. Bunjes)
  • Charité, Berlin

    • Rheumatology (PD T. Häupl, Dr. J. Ringe)
  • International

    • Universität of Natural Resources and Life Sciences, Vienna (Prof. Dr. C. Kasper)
    • Inserm U844 Montpellier (Prof. C. Jorgensen, Dr. F. Apparailly, Dr. Danièle Noel)
    • London Kennedy Institute of Rheumatology (Prof. Y. Chernajovsky, Prof. A. Nissim)

Publications

-> Publications

About The VIANNA research team